This proposal has been prepared in response to the request for application RFA ES-096-07 entitled "Biological Effects Poser Frequency EMF." In particular, we respond to the need for research on "the potential biological effects for exposure conditions such as harmonics" and for research on genetic effects of such EMFs. We propose to investigate immediate early gene transcription induced by 60-Hz electromagnetic fields (EMF) with a higher harmonic content. The existing solenoid-based magnetic field exposure system will be powered by a square-wave electric input, instead of a sine-wave electric input. We will test the hypothesis that exposure to EMFs with higher frequency- components alter expression of immediate early genes and, therefore, that there is a risk for EMF-induced adverse health effects, including cancer. Broad frequency EMFs that include harmonics in addition to 60 Hz are common n work and other environments. The current experimental database does not include frequency spectra as a variable. Occupational or domestic exposure to such fields, if biologically active, may represent a long-term health risk to humans. We will use gene transcription as a model of an EMF-induced response. The specific aim of the proposal is to identify differentially expressed known and novel immediate early genes in human HL60 or MCF7 cells following 2 mT, 3 or 24 h exposure at post-exposure times of 0 and 3 h. We have developed and successfully tested a polymerase chain reaction-based technique for the rapid complementary DNA (cDNA) screening and isolation of differentially expressed genes among randomly-selected genes from a cell-specific cDNA library in large enough quantities for sequencing.